Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models
ABSTRACT Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS componen...
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American Society for Microbiology
2016
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oai:doaj.org-article:6eb3820b05004e5d845301d5b1d30b902021-11-15T15:50:15ZDiffering Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models10.1128/mBio.00618-162150-7511https://doaj.org/article/6eb3820b05004e5d845301d5b1d30b902016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00618-16https://doaj.org/toc/2150-7511ABSTRACT Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. IMPORTANCE This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development.Tania Rivera-HernandezManisha PandeyAnna HenninghamJason ColeBiswa ChoudhuryAmanda J. CorkChristine M. GillenKhairunnisa Abdul GhaffarNicholas P. WestGuido SilvestriMichael F. GoodPeter M. MoyleIstvan TothVictor NizetMichael R. BatzloffMark J. WalkerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016) |
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DOAJ |
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DOAJ |
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EN |
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Microbiology QR1-502 |
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Microbiology QR1-502 Tania Rivera-Hernandez Manisha Pandey Anna Henningham Jason Cole Biswa Choudhury Amanda J. Cork Christine M. Gillen Khairunnisa Abdul Ghaffar Nicholas P. West Guido Silvestri Michael F. Good Peter M. Moyle Istvan Toth Victor Nizet Michael R. Batzloff Mark J. Walker Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| description |
ABSTRACT Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. IMPORTANCE This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development. |
| format |
article |
| author |
Tania Rivera-Hernandez Manisha Pandey Anna Henningham Jason Cole Biswa Choudhury Amanda J. Cork Christine M. Gillen Khairunnisa Abdul Ghaffar Nicholas P. West Guido Silvestri Michael F. Good Peter M. Moyle Istvan Toth Victor Nizet Michael R. Batzloff Mark J. Walker |
| author_facet |
Tania Rivera-Hernandez Manisha Pandey Anna Henningham Jason Cole Biswa Choudhury Amanda J. Cork Christine M. Gillen Khairunnisa Abdul Ghaffar Nicholas P. West Guido Silvestri Michael F. Good Peter M. Moyle Istvan Toth Victor Nizet Michael R. Batzloff Mark J. Walker |
| author_sort |
Tania Rivera-Hernandez |
| title |
Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| title_short |
Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| title_full |
Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| title_fullStr |
Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| title_full_unstemmed |
Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models |
| title_sort |
differing efficacies of lead group a streptococcal vaccine candidates and full-length m protein in cutaneous and invasive disease models |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://doaj.org/article/6eb3820b05004e5d845301d5b1d30b90 |
| work_keys_str_mv |
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